The Immunology and Cancer (IC) Program has been an integral part of the UCCCC for more than 25 years. It has 22 members from 6 Departments, and is supported by a total of $13,081,506 in annual peer reviewed funding (direct costs), of which $2,351,962 comes from the NCI. Over the previous funding period (encompassing 4 years). Program members have produced a total of 219 peer-reviewed cancer relevant publications, with 29% published in the highest impact journals; 18% of these were interprogrammatic and 9% were intraprogrammatic. The broad goals of the Immunology and Cancer Program are to understand the interface between the host immune system and a malignant tumor and, ultimately, to manipulate that interaction to promote immune-mediated tumor destruction in patients with cancer. It is well established that tumors can express antigens that can be recognized by specific T cells or antibodies. Identifying the reasons why a given cancer is not eliminated spontaneously should highlight the major barriers that need to be overcome in order to restore immune control over the tumor. The research themes of the program focus on understanding the mechanisms of innate immune activation and productive antigen presentation; activation and differentiation of lymphocytes into effector/memory states; trafficking into inflamed target tissues and control of local inflammation; and overcoming mechanisms of peripheral immune tolerance. Basic concepts are integrated into mouse preclinical tumor models, and novel clinical trials are performed to capitalize on this new knowledge translationally, many in collaboration with clinical investigators outside of the Program. The clinical/translational effort is supported by several key Core Facilities, in particular the Human Immunologic Monitoring-cGMP Facility. By incorporating detailed scientific endpoint monitoring into clinical studies, new key information is generated that has led to the development of new hypothesess that are interrogated back in the laboratory. Thus, the Immunology and Cancer Program is a clear example of bi-directional translational research.